Acta Pharmacologica Sinica 2006 April; 27 (4): 423-429; doi: 10.1111/j.1745-7254.2006.00296.x

Aim: To determine whether all-trans retinoic acid (atRA) acts to modulate angiotensin II (Ang II)-induced cardiac fibroblast cell growth and collagen secretion.

Methods: Cultured neonatal rat cardiac fibroblasts (CF) were used in the experiment. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to detect cell growth of the CF; and immunocytochemistry and Western blotting were used to measure the production and secretion of collagen and the expression of transforming growth factor-β₁ (TGF-β₁) by the CF.

Results: atRA (1×10^-7 to 1×10^-5 mol/L) inhibited the Ang II-induced increase in cell growth of CF (P<0.05). Ang II stimulated the secretion of collagen types I and III by the CF. This effect was blocked by AT₁ receptor antagonist losartan (1×10^-6 mol/L), but not by AT₂ receptor antagonist PD123319 (up to 1×10^-6 mol/L). Exposure of CF to atRA (1×10^-5 mol/L) attenuated the Ang II-induced increase in the secretion of collagen types I and III (P<0.05). atRA (1×10^-5 mol/L) also blocked the Ang II-induced increase in the expression of TGF-β₁.

Conclusion: atRA inhibits the Ang II-induced increase in cell growth and collagen secretion of neonatal rat CF. The effect of atRA is possibly mediated by lowering the TGF-β₁ level. These observations support the notion that atRA is a potential candidate for the prevention and therapy of cardiac remodeling.

Keywords: cardiac fibroblast; angiotensin II; all-trans retinoic acid; collagen secretion; transforming growth factor-β₁